DESCRIPTION (Applicant's Abstract): This Small Business Innovation Research Phase I project aims to investigate the feasibility of developing new compounds capable of measuring initial stages of apoptosis induction in living cells and tissues. If successful, the proposed research will provide breakthroughs needed to advance the discovery of promising new apoptosis modulating drugs for medical applications. In Phase I of this project, Marker Gene Technologies, Inc. proposes to establish the feasibility of the technology by preparing new fluorogenic peptidase substrates for the Caspase family of enzymes, for administration to living cells or tissues that either have been induced to initiate apoptosis or are of disease interest. These new substrates and the resulting detection systems will provide innovative methods to quantitate apoptosis induction and to screen for the influence of secondary drug or treatment administration. In Phase I, the new substrates will be assayed in vitro for their ability to measure specific and localized inhibition or induction of apoptosis in living cells and to do so in a cell- or tissue-specific manner. In Phase II, the substrates will be further tested as an analytical tool in vivo and in a variety of significant medical applications. PROPOSED COMMERCIAL APPLICATION: The success of this project opens up enormous commercial possibilities in the field of medical intervention in proliferative diseases such as cancer and degenerative diseasess such as Alzheimer's disease, screening of new proteins and drugs in cell-culture systems for efficacy in modulating apoptosis, and general new peptidase detection strategies. In addition, it will lead to licensable products in these areas.